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Buying time for liver patients

By Manuella Phillips

WITH time, many people suffering from acute liver failure will recover. But time is often a luxury such patients can ill afford, and the only alternative is the drastic solution of an entire organ transplant. Now scientists at the University of Rostock in Germany have developed a technique based on dialysis that gives victims of liver failure a crucial period of respite by removing lethal poisons from their blood while their livers heal themselves.

Jan Stange and Steffen Mitzner have devised a way to remove toxins, such as mercaptans and phenols, that bind to proteins in blood. These are normal by-products of metabolism but, says Mitzner, if they accumulate in the bloodstream they contribute to a build-up of fluid in the brain that eventually leads to death.

In the blood of a healthy person, the poisons bind to the protein albumin and are converted in the liver into less toxic or water-soluble compounds that are excreted in bile or by the kidneys. But if the liver is damaged – by alcohol abuse or hepatitis, for example – it can lose its ability to separate the toxins from the albumin.

The conventional way to remove poisons from blood – when a person’s kidneys fail, for example – is dialysis. In this process, blood is pumped past a semipermeable membrane, on the other side of which flows a dialysing solution containing concentrations of salts and sugars similar to those found in normal blood. While the concentrations of these useful substances are thus preserved or restored to normal, poisons with a small enough molecular size are drawn out of the blood, by osmosis.

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Unfortunately, protein-bound molecules are too big to pass through the pores of conventional dialysis membranes. But Stange and Mitzner have used a membrane with pores wide enough to allow the toxins to pass through, but too small for the proteins. In addition, they use a dialysing solution of albumin. The toxins detach themselves from the albumin in blood and bind to the albumin in the dialysing solution. This solution can then be recycled, while the blood is passed through a conventional dialysis machine to remove other toxins.

The precise mechanism of how the protein-bound toxins detach themselves from the albumin and transfer across the membrane is not fully understood. “It just works,” says Stange. The technique has been tried on 11 seriously ill patients at the Rostock University Clinic who were not expected to survive without a new liver. Seven survived without a transplant. Stange says that if the technique proves successful in other clinical trials, he expects it will be further tested in patients with chronic liver disease.

The Rostock technique is “interesting from a technological point of view”, says Robin Hughes, a biochemist in the liver unit at King’s College Hospital, London. “But its clinical value is hard to gauge.”

Competition to create artificial livers is fierce and a number of methods are being tested. The ultimate goal is to make the organs out of cultured liver cells, says Hughes. He expects the German technique to be an “interim step”.

But Stange expects the technique to be used in combination with cell cultures, so that the cells receive detoxified blood. To judge by present results, he says, the membrane technique is “at least as good”, as well as being “safer and cheaper” than any of the methods based on cell cultures.